New DNA structure found in human cells

A 'twisted knot' of DNA, known as an i-motif, has been found in living cells for the first time, raising questions about its function.

DNA can take on a variety of structures in addition to the famous double helix. One of these structures, the intercalated motif, or 'i-motif', was first observed in vitro in the lab in 1993, but whether it had any biological function was unknown.

This month, scientists from the Garvan Institute of Medical Research, University of New South Wales and the University of Sydney, Australia have published in Nature Chemistry the first evidence that i-motifs can be found in the DNA of living cells.

Professor Marcel Dinger, who co-led the research, explained the structure of the i-motif: 'The i-motif is a four-stranded 'knot' of DNA… In the knot structure, C letters on the same strand of DNA bind to each other – so this is very different from a double helix, where 'letters' on opposite strands recognise each other, and where Cs bind to Gs.'

The researchers used antibodies that were specifically designed to recognise and bind to i-motifs in human cells. By attaching a fluorescent green dye to the antibodies, the team was able to see where and when i-motifs formed in the cells' DNA.

'What excited us most is that we could see the green spots – the i-motifs – appearing and disappearing over time, so we know that they are forming, dissolving and forming again,' said Dr Mahdi Zeraati, the paper's first author. This transient nature of i-motifs is thought to partly contribute to why it has taken so long to be found in living cells.

The research offers some clues about the potential role that i-motifs play in the cell. I-motifs were most likely to form during a phase of cell division called the G1 phase, when the DNA is read prior to being replicated. I-motifs were commonly found in gene promoters: the DNA sequences that cause a gene to turn on or off, and in telomeres, the repetitive DNA sequences which protect the end of the chromosomes.

As Dr Zeraati explained: 'We think the coming and going of the i-motifs is a clue to what they do. It seems likely that they are there to help switch genes on or off, and to affect whether a gene is actively read or not.'

Professor Daniel Christ, who co-led the research, added: 'When most of us think of DNA, we think of the double helix… This new research reminds us that totally different DNA structures exist – and could well be important for our cells.'